Self-knowledge, Discriminability, and Demonstrative Thoughts

Abstract

According to content externalism, the content of our thought is partly determined by the linguistic environment responsible for it. However, there is growing skepticism about the compatibility of content externalism and self-knowledge. The skeptical position holds that, if content externalism is true, then we cannot know our own thought content because we would not be able to discriminate it from relevant alternative thought contents. This argument rests on the proposition that knowledge requires some type of discriminability. In this paper, I argue that this requirement does not apply to a particular type of demonstrative thoughts, more specifically, that in a typical case where we demonstratively denote an object without taking it as anything in particular, our secondorder judgment about our own thinking, whose content includes this use of a demonstrative, constitutes knowledge without due discriminability.

Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA) Receptors: Structure–Activity Relationships and Mechanisms of Action

“…3.1 GluN2A-selective NAMs 3.1.1 Sulfonamide series-Bettini and colleagues 50 identified the first highly selective non-competitive GluN2A inhibitors which were also the first ligands later reported to bind at the LBD GluN1/GluN2 dimer interface 51 . The prototype is TCN-201 8 (Figure 4a).…”

“…of action-The structural basis of both glycine reversal of NAM activity and GluN2A selectivity of TCN-201 and MPX-004/MPX-007 are now understood 51 . Site-directed mutagenesis and crystallography studies indicate that the TCN-201 binding site is located at the dimer interface between the two ligand binding domains ( Figure 5) at a site partially overlapping with the PAM GNE-6901 binding site (discussed below).…”

“…Site-directed mutagenesis and crystallography studies indicate that the TCN-201 binding site is located at the dimer interface between the two ligand binding domains ( Figure 5) at a site partially overlapping with the PAM GNE-6901 binding site (discussed below). In the binding pocket, both TCN-201 and a related compound (compound 6 from Bettini and colleagues 50 ) were found to fold back on themselves with stacking of the middle and the halogenated rings 51,59 ( Figure 6). The middle ring also interacts with the GluN2A-specific residue V783 which accounts for TCN-201's selectivity; this residue is replaced by phenylalanine in GluN2B and leucine in GluN2C and GluN2D which sterically hinder NAM binding.…”

“…When the NAM is bound, GluN2A V783 is displaced and, in turn, interacts sterically with GluN1 F754. This latter interaction is unfavorable and can be accommodated by glycine unbinding and opening of the GluN1 LBD to allow GluN1 F754 to move away from GluN2A V783 51 . Thus, the NAMs stabilize the open, inactive GluN1 LBD conformation.…”

Programmable nanomaterials for health-related flexible sensing electronics

“…Self-power sensing devices have been developed to meet the power demands of wearable health monitoring system. [216][217][218][219] There still needs to develop the replaceable and flexible power source with continuable and long-time output.…”